DESCRIPTION: Approximately 500,000 people die from or are permanently disabled by stroke and brain trauma each year in the U.S. The estimated cost of stroke, in terms of care and lost productivity, is $30 billion annually. There are no drugs currently available that reduce the damage caused by stroke. Nitrones and related compounds represent a new category of stroke therapeutic agents with the potential to overcome the shortcomings of other compounds evaluated for stroke. During Phase I, Centaur established an active synthetic program and a series of screening tests for both efficacy and safety aimed at identifying active nitrone related therapeutic agents TM (NRTs) for stroke. We screened over 250 NRTs and have identified potential lead and back-up compounds. The specific aim of this Phase II application is to develop a lead NRT for which an IND application would be filed for the treatment of stroke. The best NRTs discovered during Phase I will be further evaluated and developed during Phase II using the permanent middle cerebral artery occlusion stroke model. In these tests, the NRTs will be administered post-stroke and will be examined for their ability to prevent neuronal loss and learning/memory deficits.